Transferrin receptor 1
Transferrin receptor 1
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DOI：
10.1016/j.biocel.2004.02.007
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发表时间：
2004-11-01
影响因子：
4
通讯作者：
Aisen, P
中科院分区：
文献类型：
--
作者：
Aisen, P
随着转铁蛋白作为未成熟红细胞合成血红蛋白的铁源的发现，证明了细胞表面受体，即现在所知的转铁蛋白受体1，是铁从转铁蛋白输送到细胞所必需的。(这篇简短的综述不会讨论最近描述的第二种转铁蛋白受体，它的功能尚不清楚。)在接下来的几年里，转铁蛋白受体1被确定为调节大多数细胞铁摄取的守门人，并详细描述了转铁蛋白到细胞内的途径。遗传性血色素沉着症是一种进行性和毒性铁超载的疾病，HFe蛋白与转铁蛋白竞争结合受体，从而阻碍转铁蛋白对铁的摄取。HFe的突变破坏了这种竞争，从而促进了转铁蛋白及其铁进入细胞。转铁蛋白受体1的晶体结构以及转铁蛋白和HFe的晶体结构的可用性，开启了通过相关的同步加速器产生的羟基足迹和冷冻电子显微镜来研究转铁蛋白-HFe-转铁蛋白受体界面的分子图谱的研究。新出现的挑战是将结构与受体结合对铁依赖细胞内转铁蛋白的铁结合和铁释放特性的功能影响联系起来。(C)2004爱思唯尔有限公司。保留所有权利。
With the discovery that transferrin serves as the iron source for hemoglobin-synthesizing immature red blood cells came the demonstration that a cell surface receptor, now known as transferrin receptor 1, is required for iron delivery from transferrin to cells. (A recently described second transferrin receptor, with as yet poorly understood function, will not be discussed in this brief review.) In succeeding years transferrin receptor 1 was established as a gatekeeper for regulating iron uptake by most cells, and the transferrin-to-cell endocytic pathway characterized in detail. HFE, the protein incriminated in the pathogenesis of hereditary hemochromatosis, a disorder of progressive and toxic iron overload, competes with transferrin for binding to receptor, thereby impeding the uptake of iron from transferrin. Mutation of HFE destroys this competition, thus facilitating access of transferrin and its iron to cells. Availability of the crystal structure of transferrin receptor 1, along with those of transferrin and HFE, opened research on molecular mapping of the transferrin-HFE-transferrin receptor interfaces by correlated synchrotron-generated hydroxyl radical footprinting and cryo-electron microscopy. The emerging challenge is to relate structure to the functional effects of receptor binding on the iron-binding and iron-releasing properties of transferrin within the iron-dependent cell. (C) 2004 Elsevier Ltd. All rights reserved.